Summary:The purpose of this study was to determine whether, in Alzheimer disease (AD) patients, abnormalities in energy charge or phospholipid metabolism could be detected during life with quantitative phosphorus magnetic resonance spectroscopy (31P MRS). We performed in vivo31P MRS in 16 patients with a clinical diagnosis of probable AD with mild to moderate dementia severity (mean Blessed Dementia Score=17.5, range=7-37) and in 8 healthy, nondemented, age-matched, control subjects. MR studies were performed on a commercial 1.5 T MR imager using a volume head coil. We acquired brain spectra by sampling a 6-cm-thick axial slice through the cerebrum (a region that includes ~900 ml of brain tissue); we measured B-nucleoside triphosphate (B-NTP), phosphocreatine (PCr), phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (P,) concentrations, then calculated ratios of these resonances. The B-NTP, PCr, and P, resonances in AD and control subjects were not significantly different. These data indicate that brain energy stores are not depleted in AD. No significant differences were detected in the absolute measurements of PME and PDE between the AD and control groups. However, among the calculated ratios, an increase in the PME/PDE ratio of ~50%, mostly due to a decrease in the PDE signal, was statistically significant (AD PME/PDE mean=0.35, range 0.13-0.71; normal PME/PDE mean=0.22, range 0.16-0.34). We speculate that the difference in PDE reflects changes in the biophysical state of membrane phospholipids in AD.